Radioactive devices have found a host of uses in modern medicine, especially for treating cancerous growths and restenosis. Certain non-malignant growths have been shown to be responsive to radiation treatment, and may be amenable to treatment with an implantable radioactive medical device.
After balloon angioplasty, a metal tubular scaffold structure called a stent may be permanently implanted to physically hold open the repaired coronary artery. Unfortunately, up to 30% of such procedures result in narrowing or reclosure (restenosis) of the artery within six months to one year. One solution to the problem is to provide acute local, postoperative radiation treatment of the site using a catheter tipped with iridium-192 radioisotope. In this method the iridium-192-tipped catheter is placed at the arterial site for thirty to forty minutes after stent deployment and then retracted. This type of acute high dose treatment using gamma radiation has been found to substantially reduce the rate of subsequent restenosis, as noted in Wiedermann, J. G. et al., "Intracoronary Irradiation Markedly Reduces Restenosis After Balloon Angioplasty in a Porcine Model", 23 J. Am. Coll. Cardiol., 1491-1498 (May 1994) and Teirstein, P. S. et al., "Catheter-Based Radiotherapy to Inhibit Restenosis After Coronary Stenting", 336 New England Journal of Medicine, 1697-1703 (Jun. 12, 1997).
This method of irradiating the patient suffers from the hazards associated with the required high radiation intensity. In addition to the surgeon, an oncologist and a radiation physicist are typically required for the procedure. A heavily shielded lead vault is needed to separate the patient from the operating room personnel, and the task of safely inserting the catheter containing the intense source, which is on the order of about 0.75 Curies, is particularly difficult. If irregularities occur in the procedure, the surgeon has relatively little time to respond, and therefore emergency procedures must be well-rehearsed. This method, while possible in a research environment, may not be practical for many clinics and community-based hospitals.
An alternate method of addressing the restenosis problem is to embed within the structural material of the stent itself a radioactive material, such as described by Fischell et al. in U.S. Pat. No. 5,059,166 (the '166 patent) and in U.S. Pat. No. 5,176,617 (the '617 patent). The '166 and '617 patents also describe methods of electroplating a radioactive material on the structural material of the stent. These methods have certain drawbacks. Placement of radioactive material within the structural material of the stent can present fabrication difficulties with respect to radiation exposure of workers during the manufacturing process. The electroplating process may result in poor adhesion of the radioactive material, which could delaminate during insertion or stent expansion. Although electroplating is an inexpensive technique, electroplating does not work well on devices made of stainless steel or nitinol, and there are many desirable radioactive elements that cannot readily be electroplated. Also, electroplating and many other types of coating technologies, for example sputtering, cathodic arc, or magnetron sources as taught by Good, et al. in U.S. Pat. No. 5,342,283, generally require a relatively large quantity of specially fabricated and prepared feedstock material to be successfully employed. These technologies are ineffective when only a few milligrams of feedstock are available.
Another method mentioned by Fischell and investigated by Laird, J. R. et al., in "Inhibition of Neointimal Proliferation with a Beta Particle Emitting Stent", Circulation 1996; 93:529-536 (the `Laird article`), is to impregnate titanium stents with up to thirty atom percent of stable phosphorous and subsequently activate the entire stent in a nuclear reactor to form the radioisotope .sup.31 P within the titanium structural material. One of the disadvantages of the Laird method is that the massive quantity (30 atom %) of phosphorous required to achieve even 0.15 microcuries from .sup.31 P may severely alter the structural strength of the stent itself.
In the preferred embodiment of the '166 and '617 patents, the structural material in the body of the stent is alloyed with a non-radioactive precursor element and then subsequently activated in a nuclear reactor to generate the radioactive isotope. However, if the body of the stent or any similar implantable medical device (including, for example, cancer irradiation needles, shunts, vascular grafts, bone screws, and femoral stem implants) contains significant quantities of iron and/or chromium, as is true of stainless steel, for example, then neutron activation produces long-lived radioisotopes which emit a substantial quantity of gamma rays. The emission of these gamma rays is not desirable in a permanent implant because of the resulting high total body dose of radiation.
Another method for embedding the desired radioisotopes in the body of the stent is known as ion implantation. This has been described by Janicki et al. ("Production and Quality Assessment of Beta Emitting .sup.32 P Stents for Applications in Coronary Angioplasty", 42nd Annual Meeting of the Canadian College of Physicist in Medicine, Jun. 20-22, 1996, University of British Columbia, Vancouver, Canada.) and by Fischell et al. (Low-Dose, .beta.-Particle Emission From `Stent` Wire Results in Complete, Localized Inhibition of Smooth Muscle Cell Proliferation" Circulation 90 :1994) specifically for .sup.32 P-containing stents. A radioactive ion source for .sup.32 P is described in co-pending application U.S. Ser. No. 08/887,504, which is hereby incorporated by reference.
Ion implantation consists of ionizing individual atoms of the radioactive species, accelerating the charged atoms through a high voltage, and directing the resultant beam onto the surface of a device. The high velocity of the accelerated atoms causes the impinging atoms to be embedded below the surface of the device and thus to become incorporated within the body of the device. The ion implantation process may utilize a magnetic mass filter device which separates the atoms of the desired radioisotope from the large family of isotopes that may be produced when the atoms are first ionized. Since only a relatively small quantity of radioactive atoms are required to produce the desired intensity of radioactivity, it is possible to avoid the problem encountered in the Laird method, wherein a high concentration of alloying material may modify the structural strength of the device material.
While ion implantation has been successfully demonstrated to embed radioactive .sup.32 P within a stent, ion implantation of other radioactive isotope species is more difficult. For example, the radioactive isotope .sup.103 Pd requires as much as 30 times the activity level of .sup.32 P for a similar therapeutic effect, thus making the task of ion-implanting .sup.103 Pd much more difficult. In particular, the radioactive isotope feedstock must be utilized much more efficiently than usual (typically between 0.1 and 0.5%) in order to avoid accumulating large quantities of radioactive palladium waste throughout the ion implanter. Radioactive isotopes are expensive, and the waste of most of the radioactive material is both costly and hazardous because of the accumulated radioactive contamination which escapes being ion implanted into the medical device. In addition, there is also an increased risk of radiation dose to personnel who would have to periodically maintain the inefficient, radioactive evaporation apparatus.
Although numerous techniques have been devised to coat or implant radioactive material onto medical devices, none of these techniques transfer the radioactive material with a high efficiency. As a result, these techniques are inadequate, particularly when only a few milligrams of source material are available.